Abstract 8963: Mitochondrial Dysfunction in Peripheral Blood Mononuclear Cells is Associated With Heart Failure in Patients With Single Ventricle Congenital Heart Disease

Abstract

Introduction: Heart failure (HF) remains a leading cause of death and indication for heart transplant in children with single ventricle congenital heart disease (SV). The purpose of this study was to evaluate mitochondrial function in circulating peripheral blood mononuclear cells (PBMCs) from failing pediatric SV patients compared to age-matched nonfailing controls (NF). Prior data obtained at the time of cardiac transplant shows associations between SV PBMC mitochondrial function and ex-vivo high-resolution respirometry analysis conducted on permeabilized myocardial fibers, suggesting that PBMCs may be surrogates for myocardial mitochondrial function. Hypothesis: SV patients will have impaired mitochondrial respiratory capacity in circulating PBMCs. Methods: Subjects were recruited from Children’s Hospital Colorado. SV patients ages 0-18 years were included. Healthy children 0-18 years of age with normal biventricular cardiac function were included as a control group. PBMCs were isolated from whole blood (EDTA) using density gradient centrifugation in Histopaque Accuspin tubes. Oxygen consumption rates (OCR) of intact PBMCs were measured using the Seahorse XFe Bioanalyzer (Agilent). OCR is measured under 4 different conditions (Figure 1): baseline, after addition of oligomycin, after addition of carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone, and after addition of antimycin A and rotenone. Results: Baseline respiratory capacity, coupling efficiency, and mitochondrial oxygen flux were decreased in failing SV PBMCs relative to NF controls (Figure 2). Conclusions: Our results demonstrate impaired mitochondrial respiratory capacity in circulating PBMCs of pediatric SV patients relative to healthy age-matched controls. Combined with our ex vivo data showing decreased mitochondrial function in failing SV myocardium, our findings suggests PBMCs may serve as a viable non-invasive biomarker of myocardial respiratory capacity.